Irradiation induces neural precursor-cell dysfunction
Abstract
In both pediatric and adult patients, cranial radiation therapy causes a debilitating cognitive decline that is poorly understood and currently untreatable. This decline is characterized by hippocampal dysfunction, and seems to involve a radiation-induced decrease in postnatal hippocampal neurogenesis. Here we show that the deficit in neurogenesis reflects alterations in the microenvironment that regulates progenitor-cell fate, as well as a defect in the proliferative capacity of the neural progenitor-cell population. Not only is hippocampal neurogenesis ablated, but the remaining neural precursors adopt glial fates and transplants of non-irradiated neural precursor cells fail to differentiate into neurons in the irradiated hippocampus. The inhibition of neurogenesis is accompanied by marked alterations in the neurogenic microenvironment, including disruption of the microvascular angiogenesis associated with adult neurogenesis and a marked increase in the number and activation status of microglia within the neurogenic zone. These findings provide clear targets for future therapeutic interventions.
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- Authors
- Monje, M. L., Mizumatsu, S., Fike, J. R., & Palmer, T. D.
- Affiliations
- Stanford Medicine (US)
- University of California, San Francisco (US)
- Stanford University (US)
- Venue
- Nature Medicine
- Published
- 2002-08-05
- Volume
- 8
- Issue
- 9
- Pages
- 955-962
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2098137179
- Cited by
- 1,271
- References
- 35
- Citations by year
- 2026: 26 · 2025: 63 · 2024: 48 · 2023: 43 · 2022: 57 · 2021: 67 · 2020: 60 · 2019: 52 · 2018: 43 · 2017: 64 · 2016: 62 · 2015: 64 · 2014: 62 · 2013: 65 · 2012: 58
- FWCI
- 8.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH20016-05)
- National Cancer Institute (R01CA076141)
- National Institute of Neurological Disorders and Stroke (R01NS40088)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Keywords
- cranial irradiation, radiation-induced cognitive impairment, hippocampal neurogenesis, neural progenitor cells, postnatal neurogenesis, angiogenesis, microglial activation, pediatric brain tumors, radiotherapy complications
- MeSH terms
- Animals, Astrocytes, Brain, Bromodeoxyuridine, Cell Differentiation, Cell Division, Cells, Cultured, DNA Repair, Female, Neovascularization, Pathologic, Neurons, Rats, Inbred F344, Stem Cells, Microglia, Cell Transplantation, Stem Cell Transplantation, Rats
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